N. Vitoratos

Intrauterine inflammation and preterm delivery

Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Specifically, chronic amniotic fluid inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, viral infections also appear to be involved. Recently, molecular genetic techniques have helped us better understand the underlying pathophysiologic processes. This is especially important because epidemiological and experimental studies indicate that intrauterine infection and inflammation constitute a risk factor for adverse neurological outcome in preterm infants. Chronic subclinical chorioamnionitis associated with preterm birth can also modify lung development. Although no current clinical strategy is aimed at adapting the maternofetal inflammatory response, immunomodulators may serve as a future intervention in preterm embryos.

Placental growth factor (PlGF): a key to optimizing fetal growth

Abstract The needs of the uterus and the fetus for the provision of nutrients and oxygen, supplied by the blood flow, are understandably extremely high, with the circulatory system playing the most important role in this action. Abnormal vascular growth and transformation that create a high vessel resistance network have been associated with various pregnancy pathologies, including miscarriage, small for gestational age (SGA) fetuses with or without preeclampsia and intrauterine growth restriction (IUGR). Placental growth factor (PlGF) has a major role in vasculogenesis and angiogenesis in human placenta. Low concentrations of PlGF and high concentrations of its inhibitor-soluble Fms-like tyrosine kinase-1 (sFlt-1) are linked with impaired angiogenesis and placental development, leading to the above pregnancy complications. The activity of vascular endothelial growth factor (VEGF), which is the most potent of all angiogenic mediators, is partly modulated by PlGF. Although the mechanisms via which PlGF exerts its various effects are still under investigation, we herein discuss the known actions exerted by this major mediator together with its results on fetal growth.

Myomectomy during Cesarean Section

Abstract:  A patients frequent request is the simultaneous surgical removal of a previously diagnosed myoma during cesarean section. The aim of this study was to evaluate the safety and efficacy of myomectomy during cesarean section. From January 1995 until December 2004, 47 pregnant women with coexisting uterine myomas underwent cesarean section and simultaneous myomectomy. All cesarean sections were performed by residents while myomectomies were conducted by the senior staff. Intraoperative and postoperative complications such as blood loss were estimated and compared with 94 women with uterine myomas who underwent surgical delivery without removal of the fibroids. Furthermore, the length of hospitalization was compared between the two groups. Myomectomy added a mean time of 15 min to the operative time of cesarean section. No hysterectomy was performed at the time of the cesarean section. No complications were developed during the puerperium. The difference between the preoperative and postoperative hemoglobin mean value was statistically significant (P= 0.001) but did not differ between isolated cesarean and myomectomy‐combined cesarean groups. None of the patients received blood transfusion. The length of hospitalization was comparable between the two groups. Despite controversial literature data, we suggest that myomectomy during cesarean section could be generally recommended. Depending on size and location of myomas, the associated risks are similar to those of isolated cesarean section.

Maternal Plasma Leptin Levels and Their Relationship to Insulin and Glucose in Gestational-Onset Diabetes

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean ± SD 16.52 ± 5.07 ng/ml, range 10.84–27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 ± 1.47 ng/ml, range 7.28–13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.

“Reproductive” Corticotropin‐Releasing Hormone

Abstract:  Corticotropin‐releasing hormone (CRH), a 41 amino acid peptide, is an important regulatory molecule synthesized by neurons of the parvocellular and magnocellular hypothalamic paraventricular nuclei. It acts as the major physiologic corticotropin (ACTH) secretagogue. The CRH gene is located in humans on chromosome 8. The CRH hormone family has at least four ligands, two receptors (CRH‐R1 and CRH‐R2), and a binding protein (CRHbp). CRH is the principal regulator of the hypothalamic‐pituitary‐adrenal axis. Furthermore, CRH has been identified in most female reproductive tissues including the uterus, the placenta, and the ovary. CRH produced in the endometrium may participate in decidualization, implantation, and early maternal tolerance to semiallograft embryo. Placental CRH may participate in the physiology of pregnancy, in late pregnancy complications such as preterm labor and preeclampsia, and also in the onset of parturition. Ovarian CRH is involved in follicular maturation, ovulation, and luteolysis. Increased levels of unbound placental CRH may be responsible for the hypercortisolism of the second half of pregnancy. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period. This may explain the depressive states frequently observed in the postpartum period.

Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy

OBJECTIVES To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels. METHODS Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks. RESULTS The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies (p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml) compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational hypertension (2.47+/-0.81ng/ml). CONCLUSIONS Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.

Adnexal torsion during pregnancy: Report of four cases and review of the literature

Adnexal torsion is a rare cause of acute abdominal pain during pregnancy. It is frequently associated with ovarian stimulation for in vitro fertilization (IVF) or with ovarian masses, mainly of functional origin. The clinical, laboratory and imaging findings are non‐specific. The authors present four cases with adnexal torsion diagnosed during the first trimester of pregnancy. The clinical picture, the mode of diagnosis, and the therapeutic approach are discussed. In two cases, the adnexa was removed, because there was extensive hemorrhage and ischemia. In the other two cases, unwinding of the adnexa was carried out and the ovary was preserved. The diagnosis of adnexal torsion is difficult, especially during pregnancy, and occasionally remains a diagnostic dilemma. It necessitates a prompt surgical intervention, because any delay leads to irreversible ovarian necrosis, so that adnexectomy is ultimately required.

Evaluation of Serum ProlactinLevels in Patients with Endometriosisand Infertility

The aim of this study was to clarify the significance of serum prolactin concentrations in patients with infertility and endometriosis. Forty patients with infertility and laparoscopically proven endometriosis were recruited into the study. Basal serum prolactin levels and prolactin levels after TRH administration were measured. The mean basal serum prolactin concentrations were 12.5, 16.5, 19.5, and 26.5 ng/ml and those after thyrotropin-releasing hormone (TRH) administration were 88.3, 114.2, 125.3 and 138.8 ng/ml in patients with stages I, II, III and IV endometriosis, respectively. A statistically significant relationship was found between the basal serum prolactin levels as well as those after TRH injection and the stage of the endometriosis. The patients were divided in two groups. Group I consisted of 20 patients who did not receive any treatment, while group II consisted of 20 patients who were initially treated with GnRH analogues for 24 week and subsequently with several therapeutic schemes in order to improve their fecundity. The pregnancy rate was not different between the two groups. The patients, however, who did not become pregnant had higher serum prolactin concentrations after TRH administration as compared to those who conceived. We conclude that occult hyperprolactinemia may be a cause of infertility in patients with endometriosis.

Defective antioxidant mechanisms via changes in serum ceruloplasmin and total iron binding capacity of serum in women with pre-eclampsia.

OBJECTIVES The aim of this study was to investigate the role of serum ceruloplasmin, its ferroxidase activity and total iron binding capacity in women with pre-eclampsia. METHODS Thirty primigravidas between 32 and 36 weeks of gestation were studied. The subjects were divided into two groups: group A consisted of 15 normal pregnancies with a mean gestational age of 33.9 weeks, and group B consisted of 15 pre-eclamptics with a mean gestational age of 32.8 weeks. RESULTS The pre-eclamptics presented significantly higher serum ceruloplasmin levels compared to those with normal pregnancies (P<0.01), while the mean ferroxidase activity levels of ceruloplasmin did not differ significantly between the two groups (450.13+/-110.88 and 467.26+/-135.35 micromol/l/min in groups A and B, respectively). The mean+/-S.D. serum iron level (104.48+/-39.81 microg/dl) was greater whereas the total iron binding capacity (55.59+/-8.47 micromol/l) was lower in women with preeclampsia when compared to normal pregnancies (P<0.01 and P<0.0001 respectively). CONCLUSIONS Our results indicate that the plasma of pre-eclamptic women shows a loss of ferroxidase activity of ceruloplasmin as well as a reduction of total iron binding capacity. Thus, it seems that the plasma of pre-eclamptic women lacks the protective anti-oxidative action of these substances.

Controlled ovarian hyperstimulation with or without intrauterine insemination for the treatment of unexplained infertility

Objective: To evaluate whether there are any benefits from intrauterine insemination (IUI) as opposed to timed intercourse (TI) in stimulated ovarian cycles in couples with longstanding, unexplained infertility. Methods: Forty‐six couples with diagnoses of unexplained infertility were evaluated in a crossover study after a total of 141 cycles. Sixty‐seven cycles were with IUI after controlled ovarian hyperstimulation (COH) while 74 cycles were after COH and TI. Results: The pregnancy rate after COH/TI was 16.7% and after COH/IUI 45.2%. Cycle fecundity however was 8.9% after COH/TI and 25.7% after COH/IUI, which is a statistically significant difference (P < 0.05). Conclusions: A trial of human menopausal gonadotropin and IUI is justified in couples with prolonged infertility of unknown cause.